Citrus Peels Phenolic Derivatives Alleviate Benzo[α]pyrene-Induced Inflammatory Injury of Human Intestinal Epithelial Cells Through NLRP3 and AhR Signaling Pathways

Abstract

Benzo[α]pyrene (BaP) is ubiquitous in foods, and possesses a fatal cytotoxicity. In current study, ten Citrus peels (Chenpi) phenolic derivatives (CPDs) were isolated in a cell model of human intestinal epithelial (Caco-2) cells under BaP-exposure by a bio-assay guided method. Among them, methyl (3,4,5-trimethoxybenzoyl) valylphenylalaninate (Citrus peels phenolic derivative-2, CPD-2) performed the most protective activity by promoting the antiinflammatory potential on BaP-induced Caco-2 cells. CPD-2 inhibited BaP-induced intracellular ROS over-production and inflammatory epithelial cytokine, IL-4, IL-8, TNF-α, IL-1β and IL-18 over-expression, but not IL-6. CPD-2 also inhibited BaP-induced NLRP3 inflammasome and AhR signaling pathway activation. Overall, CPD-2 attenuates BaP-induced apoptotic death via promoting the antiinflammatory potentials by inhibiting the NLRP3 and AhR signaling pathways activation of Caco-2 cells. Finally, the Citrus peels phenolic derivatives was observed for the first time against BaP-induced inflammation and oxidative stress in human intestinal epithelial cells.